The object of this program project is to apply new technological advances in basic immunology, the production of monoclonal antibodies and T cell clones to help develop protocols for the induction of tissue transplantation tolerance in humans. Our preliminary studies suggest that preparation of cadaver renal transplant recipients with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) can markedly reduce, or perhaps eliminate, the requirement for chronic immunosuppressive drug therapy. The proposed project attempts to use mouse monoclonal antibodies to human T cells as new therapeutic agents (to replace the polyclonal rabbit ATG) and as new diagnostic agents (to monitor changes in T cell subsets). A variety of monoclonal antibodies to human T cells will be generated and analyzed for their capacity to identify new subsets which play important roles in transplantation immunity. We will study the mechanism of action of the suppressor cells and search for suppressive lymphokines. Cloned human suppressor cells will also be used as immunogens in order to generate mouse monoclonal antibodies to surface markers which are unique to these suppressor cell subpopulations.